The reg gene was cloned from a regenerating pancreas following surgical subtotal pancreatectomy and treatment with nicotinamide. Interventions that cause a reduction in beta-cell mass or suppression of beta-cell function (i.e., implantation of an insulinoma) result in a decrease in reg mRNA levels, while interventions that stimulate islet proliferation (i.e., removal of an insulinoma or surgical wrapping/partial occlusion of the pancreatic duct) are associated with marked increases in reg mRNA levels. Watanabe has recently shown that administration of recombinant reg to 90% depancreatized rats induces beta-cell proliferation. Furthermore, reg protein has been shown to induce DNA synthesis in isolated islets in culture as well as in islet-derived cell lines. These findings raised the possibility that reg may be an important growth and maintenance factor for pancreatic beta-cells. We hypothesis that REG may be a crucial outocrine and/or paracrine growth factor during embryogenesis as well as for maintenance of beta-cell function in the adult. The aim of this study was to further explore these hypotheses. The project has been developed in 6 different interrelated studies. 1) Cloning of the mouse pancreatic reg gene. 2) Expression study of the mouse reg gene during embryogenesis. 3) Characterization of the pattern of gene expression of the two nonallelic mouse reg genes during normal aging. 4) Reg expression study in an in vivo model of islet regeneration. 5) Effect of reg protein on pancreatic derived cell lines. 6) Gene mapping and subchromosomal localization of the human reg gene.